Abstract: TH-PO677

Calorie Intake Reduction May Prevent Progression of Diabetic Nephropathy by Suppressing Podocyte Hypertrophic Injury via mTORC1 Pathway Activation

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Minakawa, Akihiro, University of Miyazaki, Miyazaki, Japan
  • Fukuda, Akihiro, Oita University, Yufu, Oita, Japan
  • Kikuchi, Masao, University of Miyazaki, Miyazaki, Japan
  • Sato, Yuji, University of Miyazaki, Miyazaki, Japan
  • Fujimoto, Shouichi, University of Miyazaki, Miyazaki, Japan
Background

Glomerular hypertrophy is a well-established component of diabetic nephropathy. We have previously shown that a mismatch between glomerular volume and podocyte mass (reduced podocyte density) was associated with development of albuminuria and accelerated podocyte hypertrophic stress in a rat model of type 2 diabetes. Here, we tested whether calorie intake reduction prevents progression of diabetic nephropathy by suppressing podocyte hypertrophic injury.

Methods

Using the leptin-deficient Zucker diabetic fatty rat model of type 2 diabetes with ad libitum feeding, we have found increased glomerular volume and decreased podocyte density at 15 weeks. At 15 weeks, we thus divided the rats into an ad libitum diet group (n=5) and a 40% calorie intake reduction group (n=6). Urine samples were collected every 4 weeks and the rats were sacrificed at 30 weeks. We measured the urinary excretion of podocyte mRNA, urine albumin/creatinine ratio, glomerular volume, podocyte number per glomerular tuft, podocyte density, and P-S6 expression of podocytes.

Results

In the calorie intake reduction group, urine volume and blood glucose were significantly decreased by 18 weeks, albuminuria was significantly decreased by 22 weeks and urinary excretion of podocyte mRNA was decreased by 26 weeks, compared with the ad libitum diet group. At 30 weeks, in the calorie intake reduction group, podocyte number per glomerular tuft was not decreased (p=0.30), while glomerular volume tended to be decreased (12% decrease, p=0.052), podocyte density was significantly preserved (p=0.02), and P-S6 expression of podocytes was significantly decreased (p<0.01), compared to the ad libitum diet group.

Conclusion

Our results suggest that calorie intake reduction prevented the progression of diabetic nephropathy in a rat model of type 2 diabetes by suppressing podocyte hypertrophic injury via mTORC1 pathway activation. Calorie intake reduction could thus be a useful tool for slowing the progression of diabetic nephropathy.